Neurodegeneration is a pathological state that results in neural cell death. Although the causes of neurodegeneration may be diverse and not always ascertainable, a large number of neurological disorders share neurodegeneration as a common pathological state. For example, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS) all cause chronic neurodegeneration, which is characterized by a slow, progressive neural cell death over a period of several years, whereas acute neurodegeneration is characterized by a sudden onset of neural cell death as a result of ischemia, such as stroke, or trauma, such as traumatic brain injury, or as a result of axonal transection by demyelination or trauma caused, for example, by spinal cord injury or multiple sclerosis.
Neurodegeneration can also be triggered by a wide variety of neural cell insults resulting from, for example, alcohol abuse, drug addiction, exposure to neurotoxins and radiation. Evidence for neurodegeneration can even be found in dementia, epilepsy, various psychiatric disorders and as part of the normal aging process.
Regardless of the underlying cause, a growing body of evidence indicates that, once neurodegeneration is triggered, the outcome for all these disorders is invariably the same—the ultimate death of neural cells.
Stroke involves acute neurodegeneration (the rapid loss of central nervous system neural cells with attending loss of function) due to occlusion (ischemic stroke) or rupture (hemorrhage) of a blood vessel leading to or within the brain. It usually constitutes a medical emergency, since it can cause permanent neurological damage, systemic complications, and even death. Stroke is the leading cause of adult disability in the United States and Europe and it is the number two cause of death worldwide. Stroke accounts for more than one in every fifteen deaths in the U.S. and ranks third amongst all causes of death, behind heart disease and cancer (American Heart Association. Heart Disease and Stroke Statistics—2009 Update. Dallas, Tex.: American Heart Association; 2009; Rosamond et al. Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007; 115: e69-e171). Every third stroke has a fatal outcome (Häheim et al. Risk factors of stroke incidence and mortality. A 12-year follow-up of the Oslo Study. Stroke. 1993; 24(10):1484-9). About 6% of all deaths before age 65 and 10% of all deaths thereafter, are due to stroke (Donnan et al. Stroke. Lancet. 2008; 371(9624):1612-23). The statistical data therefore demonstrate that severe disability is an unfortunate, but all too frequent, outcome for many stroke victims. Indeed, stroke is the number one cause of inpatient Medicare reimbursement for long-term adult care. Total costs associated with the treatment and rehabilitation from stroke now exceed $45 billion per year and will undoubtedly continue to contribute to the overall increase in the cost of healthcare in the US as well as the other major industrialized nations.
Ischemic strokes are the most common form of stroke, accounting for over 80 percent of all strokes. They result from arterial blockage, usually due to thrombosis or less commonly due to embolism. Onset is generally abrupt and focal neurologic deficits typically ensue. About 20% of patients die within a few days, especially if the infarct is large. Another 10% of patients die within weeks of the initial stroke. Unfortunately, those who survive are usually severely disabled. Symptoms, depending on the area of the brain affected, include unilateral facial or limb weakness and sensory disturbances as well as cognitive and speech impairment. The larger the area of brain affected, the more functions are likely to be impaired. Some functional improvement may begin to occur within days and further recovery over several months is common. Nevertheless, the extent of recovery is unpredictable and generally incomplete. According to the American Stroke Association, of those who survive a stroke, 15 to 30% are permanently disabled, and 20% require institutional care three months after onset (Harmsen et al. Long-term risk factors for stroke: twenty-eight years of follow-up of 7457 middle-aged men in Göteborg, Sweden. Stroke. 2006; 37(7):1663-7).
Ischemic stroke leads to a core lesion, in which nerve cells die within minutes of oxygen deprivation, and a surrounding penumbra, a region that receives some blood-flow and therefore some oxygen, but less than normal. Cell death proceeds more slowly in the ischemic penumbra, typically over several hours, and is caused by variable anoxia and by toxic substances generated by the ischemic cascade and the release of glutamate in the core lesion. Current therapeutic interventions thus mainly target the alleviation of the injurious conditions in the stroke penumbra.
Treatments for acute ischemic stroke remain however limited.
Since brain damage occurs as a result of a reduction in blood flow to the brain, current therapies aim to remove the arterial blockage by either dissolving the clot (thrombolysis) or by removing the clot mechanically (thrombectomy). The faster blood flow is restored, the fewer brain cells die and the greater the chance that permanent sequelae can be averted.
At present, only two treatments are FDA approved for stroke in the United States:                Recombinant tissue plasminogen activator (rt-PA; Genentech), a drug that dissolves the arterial clot; and        The Merci Retrieval System (Concentric Medical Inc.) and Penumbra System (Penumbra Inc.), a device that mechanically removes blood clots.        
All the above therapeutic approaches have major limitations.
To be effective, therapy with thrombolytic agents must be performed within 3 to 4.5 hours of symptom onset which means only about 3% of patients with acute ischemic stroke receive effective rt-PA therapy. In addition, thrombolytic therapies carry a substantially increased risk of cerebral hemorrhage, which further limits their use in some individuals.
For the foregoing reasons, there is an unmet, urgent need in the art for safe and effective therapies that mitigate and/or prevent neurodegeneration, and especially neurodegeneration caused by ischemia.